It is planned to pursue in more depth the biochemical basis for the resistance to several hepatotoxins shown by putative preneoplastic liver cell populations. This will be done by a combined in vivo-in vitro approach. It is also proposed to explore how the options of early preneoplastic nodules, persistence or remodelling, can be influenced by diet, nucleotide analogues and other modulations. Also, it is planned to begin to study whether known mutagens can accelerate the development of neoplasia from hyperplastic nodules.